Polystyrene sulfonate containing opthalmic solutions

ABSTRACT

An opthalmic solution is provided for treatment of &#39;&#39;&#39;&#39;dry eye&#39;&#39;&#39;&#39;, providing lubricating and cushioning effects for traumatized eyes, including trauma caused by the wearing of hard or gel-type contact lenses, and as a carrier for opthalmic medicaments. The solution is an aqueous solution of polystyrene sulfonate, optionally and preferably including polyethylene glycol, and other optional ingredients.

United States Patent [1 1 Rankin Sept. 23, 1975 POLYSTYRENE SULFONATECONTAINING OPTHALMIC SOLUTIONS [75] Inventor: Billy F. Rankin,Rockvill'e, Md.

[73] Assignee: Burton, Parsons and Company, Inc.,

Washington, DC.

22 Filed: July 27, 1973 21 Appl. No.: 383,286

3,767,788 10/1973 Rankin ..424/78 OTHER PUBLICATIONS Chemical Abstracts,54: 1802521 (1960). Chemical Abstracts, 63: 2857b (1965).

Primary Examiner-Leonard Schenkman Attorney, Agent, or Firm-Fidelman,Wolffe & Leitner [57] ABSTRACT An opthalmic solution is provided fortreatment of dry eye, providing lubricating and cushioning effects fortraumatized eyes, including trauma caused by the wearing of hard orgel-type contact lenses, and as a carrier for opthalmic medicaments. Thesolution is an aqueous solution of polystyrene sulfonate, optionally andpreferably including polyethylene glycol, and other optionalingredients.

10 Claims, No Drawings POLYSTYRENE SULFONATE CONTAINING OPTHALMICSOLUTIONS lates to an opthalmic solution useful as a cleaning, lu-

bricating and cushioning agent for both hard and geltype contact lenses.The invention also relates to the attainment of all the foregoingfunctions without optical interference and with a solution which may bereadily buffered to any convenient pH. The invention further relates toan opthalmic solution having bactericidal activity.

Heretofore, opthalmic solutions have generally conformed to the generalspecifications required for all such intended utilizations in thetreatment of the eye.

Such solutions have generally been isotonic, buffered to therequired pH,sterile and have contained additives for improved viscosity and longerretention in the eye. However, with many of such solutions, the problemsof dosage, irritation to the eye, stability and occular responsepersist.

Many attempts have been made to resolve these problems by modifyingexisting formulas, using different forms of eye-treating substances, orusing bases immiscible with aqueous solutions. Such attempts have addedlittle to the performance qualities of the products.

It is accordingly an object of the present invention to provide amultipurpose opthalmic solution, suitable for general utilization in theeye of both humans and domestic animals.

A further object of the present invention is the provision of suchsolutions which can be readily modified for particular purposes andutilizations, including the introduction into the eye and the retentiontherein, of op- .thalmic medicaments, the provision of a wetting agentwhich serves as an artificial tear for the treatment of dry eye, or acushioning or lubricating agent for an injured or surgically treatedeye, as a cleaning, lubricating and cushioning agent for utilization inconjunction with both hard and gel-type contact lenses and the like.These and still other objects, as will become apparent from thefollowing disclosure, are attained by the composition of the presentinvention which, in its broadest terms, comprises a polystyrenesulfonate polymer having a molecular weight of from about 75,000 toabout 10,000,000, water, and, optionally, a polyalkylene glycol,preferably polyethylene glycol or polypropylene glycol, and havinga-molecular weight of about from Polystyrene sulfonates are known toexhibit excellent lubricating characteristics in aqueous solution andare 'freely soluble in water without degradation. Wide ranges ofmolecular weights are available. In the present'invention, these can befrom 75,000 up to several million, e.g. 10,000,000 or even greater. Themedium molecular weight materials are preferred in the present inventionand a range of 500,000 to 1,000,000 has been found particularly useful.Most preferred is a polystyrene sulfonate having a molecular weight ofabout 75,000. Such resins have extraordinary thickening action in water,even in the presence of salts. The thickening power increases sharplywith both concentration and molecular weight. Thus, to attain thedesired viscosity, substantially less polystyrene sulfonate polymer isrequired fora relatively higher weight that would be the case whenalower molecular weight polymer is utilized. In addition, the highermolecular weights result in a higher strength lubricating film insolutions due'to orientation of polymer molecules. The concentration ofthe polystyrene sulfonate polymer will vary in the present inventionwith the molecular weight to provide a viscosity of from 0 to about30,000 cps at 20C. as measured by Brookfield Viscosimeter, whereviscosities of from 0 to about 200 cps are measured using the ultra-lowviscosity adapter rotated at a speed of 0.6 rpm, and viscosities greaterthan about 200 cps are measured withja number 6 spindle rotated at 10rpm. Such viscosities will ordinarily be obtained when the concentrationis within the range of about 0.05 to 20.0

As used in the present disclosure, the term polystyrene sulfonate isintended as a convenient term to denote the class of polymers which ischaracterized by the polymerization of alkenyl aromatic sulfonates orthe sulfonation of polymers of alkenyl aromatics and, as such, is notlimited to the literal polystyrene sulfonates,

but is also inclusive of copolymers of styrene sulfonate and bothhomopolymers and copolymers of styrene sulfonate analogsas well. It isalso intended that the wide variety of polymers produced by sulfonationof alkenyl aromatic containing polymers be included as well.

The polystyrene: sulfonate polymers as thus defined are a wellknown'elass of polymers, many variations of which are commerciallyavailable. The polymerization techniques for the preparation of suchmaterials are similarly well known to those of ordinary skill in the artand many variations of such techniques are similarly in practice incommerce. y

The water soluble, linear, high molecular weight polymer sulfonates withwhich this invention is concerned correspond to addition polymers ofmonoalkenylaromatic sulfonates having the formula:

wherein I Ar is a divalent aromatic radical selected from the groupconsisting of hydrocarbon radicals and nu-' Specific examples ofsulfonates which are used in accordance with this invention arewater-soluble, linear. high molecular weight polymers of styrenesulfonicacids, oz-methylstyrenesulfonic acids, ar-methylstyrenesulfonic acids,ar-dimethylstyrenesulfonic acids, a,ar-dimethylstyrenesulfonic acids,ar-ethylstyrenesulfonic acids, ar-isopropylstyrenesulfonic acids,vinylnaphthalenesulfonic acids, ar-chlorostyrenesulfonic acids,ar-dichlorostyrenesulfonic acids, ar-chloroar-methylstyrenesulfonicacids, and the water soluble salts of such resin sulfonic acids.

The term sulfonate is used herein to mean the free sulfonic acid and itssalts. M in the foregoing formula being a cation, including hydrogen andmetal, ammonium, amine and like salt-forming cations. Specific examples,for purpose of illustration and not of limitation, of suitable salts arethe sodium, calcium, potassium, ammonium and amine salts of the polymersulfonates.

The addition polymers correspond to homopolymers ofthemonoalkenylaromatic sulfonates, copolymers of two or more suchsulfonates and one or more of other monoethylenically unsaturatedmonomers wherein the monoalkenylaromatic sulfonate is at least 60percent by weight of the total polymer. In the latter such polymers,units corresponding to a monoalkenylaromatic sulfonate are areadditionally combined with units corresponding to one or more kinds ofmonoethylenically unsaturated compounds, examples of which, for purposesof illustration-and not of limitation, are styrene, -methylstyrene,ar-methylstyrenes, ardimethylstyrenes, ,ar-dimethylstyrenes,arethylstyrenes, ar-isopropylstyrenes, vinylnaphthalenes,ar-chlorostyrenes, ar-dichlorostyrenes, ar-chloro-armethylstyrenes,isobutylene, ethylenically unsaturated esters, e.g 1-12 carbon atomalkyl esters of acrylic or methacrylic acids, vinyl esters of fattyacids such as vinyl acetate, vinyl chloride, vinylidene chloride, methylisopropenyl ketone, methyl vinyl ether, and acrylonitrile.

The term water soluble is used herein to mean that the polymersulfonates form true solutions in pure water, which solutions are freeof gel particles and infinitely dilutable with water.

By the term linear", it is meant that the polymeric chain is free ornearly free of crosslinkages. A water soluble polymer sulfonate isregarded as linear for practical purposes of this invention if its watersolution is free of gels, infinitely dilutable with water, andfilterable through ordinary filter paper (Whatmans Number l) withoutloss of viscosity.

The water soluble, linear, high molecular weight polymer sulfonates foruse in this invention are obtained either by polymerization of thecorresponding monoethylenically unsaturated monomers including amonoalkenylaromatic sulfonate or by sulfonation of a starting polymer ofmonoethylenically unsaturated monomers including a polymericallycombined monoalkenylaromatic hydrocarbon or nuclear chlorinatedmonoalkenylaromatic hydrocarbon. I

When the polymer sulfonates are obtained by sulfonation of amonoalkenylaromatic polymer resin, the resin starting material is atoluene-soluble, thermoplastic, linear, high molecular weight additionpolymer of a monoalkenyl aromatic hydrocarbon or nuclear chlorinatedmonoalkenylaromatic hydrocarbon having the general formula:

wherein H Ar is a monovalent aromatic hydrocarbon or nuclear chlorinatedhydrocarbon radical having its valence bond on a carbon atom of asulfonatable aromatic nucleus,

R is hydrogen or a methyl radical,

and the other symbols have their usual meanings. By sulfonatable, it ismeant that the nucleus of the aromatic radical has at least one hydrogeratom replaceable by the sulfonic acid group by reaction with sulfonationagents such as sulfuric acid and sulfur trioxide.

Examples of such monoalkenylaromatic polymers are the solid homopolymersof styrene, a methylstyrene, ar-methylstyrenes (ar-vinyltoluenes),ardimethylstyrenes, a,ar-dimethylstyrenes; arethylstyrenes,vinylnaphthalenes, and archlorostyrenes; copolymers of two or more ofsuch monoalkenylaromatic compounds, e.g. copolymers of styrene andar-vinyltoluene and copolymers of styrene and a-methylstyrene; andcopolymers of a major proportion of one or more of suchmonoalkenylaromatic compounds such as monoethylenically unsaturatedhydrocarbons, e.g. isobutylene, monoethylenically unsaturated esters,e.g. l-l2 carbon atom alkyl esters of acrylic or methacrylic acid, andacrylonitrile.

When the polymer sulfonates for use in this invention are made bysulfonation of monoalkenylaromatic hydrocarbon or other nuclearchlorinated hydrocarbons, the starting polymers are furthercharacterized as being linear, i.e. free of crosslinkages and havinghigh molecular weight. Moreover, it is necessary that the means andmethod of sulfonation of the starting monoalkenylaromatic polymers besuch that the resulting polymer sulfonates are water soluble, linear,high molecular weight products.

Methods are already known per se' for making polymer sulfonatesconforming to the above-described characteristics. However, it will beunderstood by those skilled in the art that methods of making polymersulfonites do not invariably produce products having the characteristicsset forth above. It is the polymer sulfonate that it controlling in thepresent invention and not the procedure by which it is prepared.

Aqueous solutions of the polystyrene sulfonate resins have a low levelof oral toxicity and an extreme level of compatibility in contact withthe skin or in the eye They are also characterized by a high level ofpituitousness and an extraordinarily high degree of pseudoplasticity.The solutions are highly stable through a wide range of temperatures andcan tolerate extremely wide variations in pH.

Because of the strong ionic bonding affinity of the sutfonate group inthe polystyrene sulfonate chain, the resin solutions will form ionicsalts and association complexes with a wide variety of materials. Suchionic salts association complexes per se often exhibit propertiesmarkedly different from either component alone, but is has been foundthat the resin will give up associated materials when introduced intothe eye. The dissociation in vivo may result from an ionization effectproduced by the materials with which the solutions are contacted, e.g.,various salts occurring in tears and the like.

Because of the high levels of pseudoplasticity and pituitousness ofpolystyrene sulfonate aqueous solu'- tions, it is highly desirable toinclude in the solution a material which will render a plasticizingeffect. In addition, it is also desirable to include a humectant whichwill enhance fluid retention over the course of long term usage in theeye. These functions are provided by the inclusion in the solution of apolyalkylene glycol. The preferred polyalkylene glycol is polyethyleneglycol, such as the Carbowaxes, as supplied by Carbide and'CarbonChemicals Company. Such materials have molecular weights ranging fromabout 400 up to as much as about 6,000. Particularly preferred in thecompositions of the preferred invention is polyethylene glycol havingmolecular weight of about 4,000, although this preferance is primarilybecause of the ready availability and convenience of processing of theparticular material. Polyglycols containing other alkylene groups can beutilized, such as polypropylene'glycols and the like, but such materialsare often not as readily available, and for this reason alone are notparticularly preferred in the present invention. The polyalkylene glycolcan be present in amounts ranging up to 5,000, preferably 500 to 5,000,weight percent based on the weight of the polystyrene sulfonate polymer.Less than about 100% by weight can occasionally result in insufficientwater retention and plasticizing effect, with concomittent drying of theeye and irritation of occular tissue, while amounts greater than about5,000 weight percent can exhibit a salting out effect, with'theformation of waxy solid globules or particles which can be irritating tooccular tissue.

The basic opthalmic solution of the present invention, i.e. the aqueoussolution of polystyrene sulfonate and polyalkylene glycol, is useful perse in a number of contexts. Primary among these is the provision of asynthetic mucous layer, which serves to clean and lubricate the eye,serving as a wetting agent and artificial tear for the treatment of dryeye or to provide a cushioning and lubricating effect in an injured orsurgically treated eye. A related effect is the cleaning, lubricatingand cushioning effects attained when the solution of the presentinvention is used in conjunction with contact lenses, of both the hardresin and gel type. Representative of the problems generally applicableto each of the foregoing usages is the use of the opthalmic basesolution of the present invention in conjunction with gel-type contactlenses, and accordingly, the use of the solution will be discussed withparticular reference thereto.

The advent of the. gel contact lens has generated entirely newrequirements for contact lens treating solutions and entirely newproblems in hygenic handling and care for the lenses. In contrast to themore common hard type lens, usually made of polymethylmethacrylate, thegel lens will absorb relatively large proportions of water to form asoft, pliable material which has a tendency to fray. The gel is athree-dimensional lattice formed by the polymerization of glycol estersand diesters of acrylic acids. The glycol moieties of the moleculesimparts a strong hydrophilic character to the lattice, with theconsequent ability to absorb rather large amounts of water. By utilizingthe unique properties of these lenses, new therapeutic options arepresented for the treatment of occular debilities. Since the lens per serepresents only the environment of use of the composition, a morecomplete discussion of its physical parameters need not be repeatedhere. A discussion of the gel contact lens, including both thepreparation and use thereof occurs in Augenoptika, Heft 6, 1965, pages 5and 6, Vienna, austria, which reports a paper delivered by MaximillinaDreyfus at the 15th WVA annual meeting.

One characteristic peculiar to the gel lens is the requirement thattreating solutions contain no component that can become entrained in thelattice of the gel, since such materials tend to accumulate and becomeirritating to the occular tissue. The lens does, however, require acleaning and lubricating solution to cushion the occular tissue fromdirect contact with the lens. The requirement for a cleaning action isshared by the gel-type lens with hard lenses and with synthetic tearsand other such opthalmic solutions. The exposure of the .eye to variousatmospheric pollutants, such as smoke, dust, pollen, noxious andirritating gases and the like can create severe discomfort andirritation, particularly in situations where the pollutants collect inthe natural or artificial tear film to persist for materials must becompatible with the gel and with occular tissue and not interfere withthe physio-chemical balance of the precorneal films. The attainment ofthese objectives is illustrated by the following example:

EXAMPLE I Polyethylene Polystyrene Distilled glycol sulfonate water 9.00gms 0.30gms 300.00 ml The solution is utilized to clean and hydrategel-type contact lenses by immersingeach lens in sufficient of thesolution to completelycover the lens. Full hydration is effected inabout l-l0 minutes. At the end of the immersion, the lens is lightlyrubbed between the fingers and rinsed with water. Each lens is examinedand was found to be fully hydrated and optically clear. The lenses arethen implaced in human eyes in conventional fashion and are left inplace for periods of 12 to 17 hours without noticeable irritation. Indry environments or drafts, some subjects flush the lenses while inplace with small increments of the solution (which is found toeffectively clean and. rehydrate the lenses), whereby the toleranceperiod of the subject is enhanced and any drying problem alleviated.

By comparison, conventional lens wetting solutions of types commerciallyavailable are found to provide inferior cleaning and the ingredientsocclude in the lens and cause irritation of the occular tissues.

In addition to the foregoing tests, both the solution of the presentinvention and the commercially available lens solution of US. Pat. No.3,171,752 were tested for retention in the eye in the following fashion:

A minor amount of fluorescein dye was incorporated into each solution.One solution was placed in one eye, the other solution in the other eye,of a number of rabbits. Examination of the eyes using an ultra-violetlight source gave a quantitative base measure of the amount of solutionpresent. Periodic repetitions of the examination revealed that thissolution was gradually lost in either case, but that the commercialsolution was retained much less effectively. The eyes treated with thesolution of this example retained at one and one-half hours the sameamount of solution as did the eyes treated with the commercial solutionat twenty-five minutes. Details of the fluorophotometric determinationcan be foundin Waltman et al., Investigative pthalmology, Vol. 9, No. 4,pp. 247-249, April, 1970.

In no case, including both the utilization of the geltype contact lensin the human eye or the solution alone in the eyes of test rabbits, wasany evidence of irritation of the eye found to result from the solutionof the present example. a

In addition to the per se usefulness of the opthalmic solution of thepresent invention as illustrated in the foregoing Example I, theopthalmic solution of the present invention finds an additional area ofbroad utility as a carrier for opthalmic treating materials such asmedicaments (particularly those requiring an acid pH). The higheffectiveness of the opthalmic solution of the present invention isbelieved due to the strong ionic bonding affinitiy of the sulfonategroup of the polystyrene sulfonate chain. When combined with theopthalmic solution of the present invention, opthalmic medicaments arefound to exhibit a much greater retention on orbital tissue and resultsin a longer duration of medicament activity. In addition, the degree ofretention attained permits the use of smaller amounts of the eyetreating substances than has been found heretofore possible whilemanitaining the necessary levels of effectiveness. Examples ofmedicaments with which the carrier can be used are:

Pilocarpine, HCL

Hydrocortisone USP (alcohol) Hydrocortisone Acetate Prednisolong Acetateand other cortisones Neomycin Sulfate Bacitracin PenicillinSulfamerazine Sodium sulfacetamide Sulfadizaine Sulfasoxozone and othersulfa derivatives Scopolamine hydrobromide Epinephrine bitrartratePhenylephrine HCl or other derivatives Prostigmin bromide Pilocarpine(any of the salts) ldoxuridine Antipyrine Naphthazoline HCl Antazolinephosphate The foregoing list is intended to be merely exemplary. As thelist illustrates, the opthalmic solution-of the present invention can beutilized as acarrier for substances such as antibiotics. mydriatics.biotics. antihistamines, and the like. The amount of eye treatingsubstances used with the composition of the present-invention dependsupon thenature of thissubstancepr substances employed and the responseof the individual receiving treatment. Typically, up to 500% or evenmore, based on the weight of the polyethylene oxide, of the eyetreatment medicament can beuse'd.

When the eye treating substance or substances are those requiring anacid pH, one or more acids can be present in amounts sufficient tomaintain the solutions ata pH ofless than 7 and as low as about 3. Anexample of an acid which can be used with eye treating sub stances suchas medicaments requiring an acid pH is boric acid. However, many eyetreating substances must be maintained in a basic or neutral medium. Inthese instances, one or more pH buffers such as sodium borate is addedto maintain a solution of a neutral or slightly basic pH. Typically, thebuffering substances present in an amount sufficient to maintain the pHat the desired level are from between about 7.4 and about 8.2, andpreferably at about 7.6. Other buffering compositions can be used aswell, including a combination of phosphates such as, for example,monosodium phosphate' and disodium phosphate to provide both acid andbase control. Other phosphates, acetates and carbonates can besubstituted for the phosphates mentioned above provided they arecompatible with the eye. Specifically, the amount of buffering additionscan range from about 0 to 4%, preferably about 0.2% for the dibasiccomponent, and from about 0 to about 0.5% for the mono-basic component,wherein the percentages are by weight based upon the total weight of theoverall composition, with the ratio of components balanced to, provideproper pH for the overall composition.

The utilization of the opthalmic solution of the present invention asthe carrier for the opthalmic medicaments is illustrated by thefollowing example:

EXAMPLE II.

The following composition is illustrative of the utilization of thecomposition of the present invention as a carrier for medicaments: apolystyrene sulfonate polymer having a molecular weight of about 700,000(National Starches and Chemical Corp. Versa-TL-700), and a polyethyleneglycol having a molecular weight of about 4,000 (Carbowax 4000) aredissolved in distilled water in the following proportions:

I Polystyrene sulfonatc 9.00 gm Ethylene oxide polymer 0.30 gmsDistilled Water 300.00 ml To the base solution. there are then added6.00 gm of pilocarpine HCl and 3.00 gm of boric acid. Both the salt andthe acid dissolve readily in this solution.

The foregoing formulation is utilized in the treatment of glaucomapatients who has previously required four standard pilocarpinetreatments per day. It is found that three treatments with theformulation of the present invention provides the same therapeuticeffects as the four standard treatments. Studies on normal eyes of bothanimals and humans, after the fashion indicated in Example I, showed noadverse effects after prolonged application periods, and a much longerperiod of retention-in the eye for each application.

Whatever the contemplated utilization of the opthalmic solution of thepresent invention, it can be desirable to include in the solution one ormore of a variety of secondary additives as hereinafter described infuller detail. For example:

Highly compatible cellulose derivatives of a variety soluble in water,such as for example, methyl cellulose, hydroxyethyl cellulose,hydroxypropyl cellulose, carboxymethyl cellulose, hydroxypropyl methylcellulose and the like, can be included in the solution to act as amechanical buffer or as a viscosity control agent.

These can also be used to maintainthe viscosity of the cient to maintainviscosity of the overall composition at the desired level.

The composition of the invention can also contain one or more eyecompatible biocides, such as thimero sal (sodiumethylmercurithiosalicylate), and the di-",trior tetradosiumethylenediamine tetraacetates. The percentages of such biocides canvary'over a broad range, but typically do not exceed aboutl% by weightof the overall composition.

In addition, the composition of the present invention can also containone or more eye compatible non-ionic surfactants in amounts varying overa wide range (but typically in amounts up to about 0.5% by weight) inorder to provide product stability. An example of the surfactants whichcan be utilized are Tergitol 155 9 (Carbide and Carbon Chemicals Co.);Pluronic F68 (Wyandotte Chemical Corp., Michigan Alkali Division);Tweens of H.L.B. value of 11 or higher (Atlas' Powder Company).

Still another subsidiary component which can be added to the opthalmicsolutions of the present invention includes polyvinyl pyrrolidone (suchas Plasdone C, supplied by Entira Chemicals, division of CAP Corp.)which performs a number of desirable functions. Polyvinyl pyrrolidone(PVP) acts as a detoxicant, binding anti-toxins present in eye fluidsand rendering them harmless. PVP also acts to protect the solution bypreventing its breakdown because of particle agglomeration and acts as ademulcent lubricant by a combination of adhesive and lubricatingproperties which aid in the spreading of the viscous solution. The PVPalso operates to prevent blepharospasm (involuntary eyelid contraction),but has little effect on an overall composition viscosity. PVP isdesirably present in an amount of from 0.5 to 10.0 weight percent basedon the overall solution.

The foregoing illustrations of secondary additives for the opthalmicsolution of the present invention are intended to be merely exemplary ofthe more common of the additives to opthalmic solutions well known tothose of ordinary skill in the art. It should accordingly be understoodthat such additives are not required for effective operation of theopthalmic solution of the present invention, nor is it intended by theenumeration of certain additives to exclude others.

While the opthalmic solution of the present invention is readily formedby simply combining the ingredients, the polystyrene sulfonate materialcan occasionally present difficulties in readily dissolving due to theforniation of lumps. Such difficulties can be avoided by the utilizationof the following technique: an increment of distilled water sufficientto dissolve the constitutents of the composition is placed in astainless steel container and heated to about 50C. If a surfactant isincluded in a composition, it is dissolved first in distilled water byagitation, e.g. with a dispersing mixer which has a variable speedcontrol set at a low speed.

Any medicament (such as pilocarpine HCl, pH buffers) and thepolyalkylene glycol (such as Carbowax 4,000) and other additives (suchas biocides and the like) are then dissolved with medium speedagitation. in the water/surfactant mixture, following which the poly-.vinyl pyrrolidone is added-with high-speed mixing and agitation. If acellulosic derivative mechanical buffer is utilized, it is sifted slowlyinto the vortex created by the.

agitator at high'speed. When thecellulosic substance is completelydispersed, the polystyrene sulfonate is sifted slowly into the vortex athigh agitation,-until the resin appears to be climbing up the agitatorshaft, at

which time the speed is reduced to l00.to 200 rpms. Agitation is thencontinued until the resin is completely dissolved in the solution,typically from 2 to 6 hours." Additional distilled water is then addedto bring the solution up to volume. When some componentsare temperaturesensitive, the product may be sterilized after EXAMPLE lll As anillustration of the composition of the present invention containing theaforementioned secondary additives, the following composition wasprepared on a relatively large scale: v v

bactcriocide (Thimerosal, 1071) cc disodium phosphate i200 gmspolyethylene glycol (MW. 4,000) 6000 gms polyvinyl pyrrolidone 3000 gmsdisodium ethylenediamine- I tetracetate 600 gms non-ionic surfactant 132gms hydroxy ethyl cellulose (MW 52.000) 3000 gms polystyrene sulfonate(Versa-TL-700) 3000 gms distilled water gallons The solution formed fromthe foregoing components was clear and free of polymer globules and wasfound to have a pH of about 7.3 and a viscosity of about 150 cps.

The solution was utilized as a wetting, cleaning and cushioning mediumby a number of pateints using hardtype, polymethyl methacrylate contactlenses. With patients who had previously worn the lenses, greater comfort and tolerance were reported, even by those who had previouslyexperienced difficulty with the lenses. Most patients reported that theywere able to wear their lenses for greater periods of time than hadpreviously been possible, regardless of the type of wetting solutionthey had used before. With patients who had not previously worn contactlenses, the solution of the present invention dramatically reduced theproblems of lens delivery and greatly accelerated the adaptation of Ithe patients to the use of the lenses. In all the trials, no

adverse side effects or irritation was noted either subjectively or byclinical examination.

It has been noted that in the utilization of the opthalmic solution ofthe present invention with contact lenses, certain ranges of viscosityprovide better results than others. For example, with hard-type lenses,the best results are attained at a viscosity of about 30 to 200 cps andthat range is accordingly preferred for such usage. The most preferredviscosity for use with hard-type lenses is about 150 cps. Withthegel-type lens, the most effective (and hence the preferred) viscositieslie in the range of about to 30cps, with values of about being mostpreferred. No variation of effectiveness with viscosity has been notedwhen the solution is used as a carrier for medicaments or as a synthetictear or the like.

It should be noted that a viscosity of zero as measured is a result ofthe limitations of the available techniques and apparatus and does notrepresent such an anomaly as it might superficially appear. It should befurther noted that all designations of viscosity appearing hereinrepresent the values as obtained with the Brookfield Viscosimeter whereall values below 200 are obtained with the ultra-low viscosity adapterrotated at 0.6 rpm and all values above 200 are obtained with a number 6spindle at 10 rpm. For values ranging from about 175 to 250 cps, resultsobtained by the two differing adaptations are generally comparable inthe case of the present solutions.

A further example of the effectiveness of the composition of the presentinvention occurs primarily in the area of opthamologic diagnosis, whereit is conventional to apply fluorescein or a comparable material,dissolved in a carrier, to the eye. After allowing the dye to penetratethe tissues of the eye, an examination is conducted by visual inspectionwith the aid of an ultraviolet light source, which causes the dye toflouresce. It has been found that when the opthalmic solution of thepresent invention is utilized as the carrier, the dye is absorbed insubstantially greater proportions and at a much faster rate than hasbeen possible with the compositions of the prior art. Accordingly,solutions of fluorescent dyes in the opthalmic solution of the presentinvention are of great aid in the examination of the eye.

While certain specific considerations have been disclosed and discussedherein, such have been offered solely to exemplify the present inventionand should in no way be construed as limiting. The proper scope andnature of the invention is set forth in the following claims.

What is claimed is:

1. An ophthalmic composition useful for providing lubricating andcushioning effects on traumatized eyes cmprising an aqueous solution ofa water soluble styrene sulfonate polymer having a molecular weight ofabout 75,000 to about 10,000,000 in an amount of from about 0.05 toabout 20 weight percent sufficient to provide a viscosity of from about0 to about 30,000 cps., and from about to about 5000 weight percentbased on the styrene sulfonate polymer of a polyalkylene glycol having amolecular weight of from about 400 to about 6000 selected from the groupconsisting of polyethylene glycol and polypropylene glycol.

2 The composition of claim 1 wherein said styrene sulfonate polymer hasa molecular weight of about 500,000 to 1,000,000.

3. The composition of claim 1 wherein said styrene sulfonate polymer hasa molecular weight of about 750,000.

4. The composition of claim 1 wherein said polyalkylene glycol ispolyethylene glygol.

5. The composition of claim 4 wherein said polyethylene glycol has amolecular weight of about 4,000.

6. The composition of claim 1 wherein said aqueous solution furthercomprises an eye compatible pH buffer in an amount effective to bufferthe pH of said solution to about 7.4 to 8.2.

7. The composition of claim 6 wherein said buffer is boric acid.

8. The composition of claim 6 wherein said buffer is a combination ofmono-sodium and di-sodium phosphates.

9. The composition of claim 1 wherein said aqueous solution furthercomprises us to about 1 percent by weight of an eye compatible biocide.

10. The composition of claim 1 wherein said aqueous solution furthercomprises up to about 5 percent by weight polyvinyl pyrrolidone.

1. AN OPHTHAMIC COMPOSITION USEFUL FOR PROVIDING LUBRICATING ANDCUSHIONING EFFECTS ON TRAUMATIZED EYES COMPRISING AN AQUEOUS SOLUTION OFA WATER SOLUBLE STYRENE SULFONATE POLYMER HAVING A MOLECULAR WEIGHT OFABOUT 75,000 TO ABOUT 10,000,000 IN AN AMOUNT OF FROM ABOUT 0.05 TOABOUT 20 WEIGHT PERCENT SUFFICIENT TO PROVIDE A VICOSITY OF FROM ABOUT 0TO ABOUT 30,000 CPS., AND FROM ABOUT 100 TO ABOUT 5000 WEIGHT PERCENTBASED ON THE STYRENE SULFONATE POLYMER OF A POLYALKYLENE GLYCOL HAVING AMOLECULAR WEIGHT OF FROM ABOUT 400 TO ABOUT 6000 SELECTED FROM THE ROUPCONSISTING OF POLYETHYLENE GLYCOL AND POLYPROPYLENE GLYCOL.
 2. Thecomposition of claim 1 wherein said styrene sulfonate polymer has amolecular weight of about 500,000 to 1,000,000.
 3. The composition ofclaim 1 wherein said styrene sulfonate polymer has a molecular weight ofabout 750,000.
 4. The composition of claim 1 wherein said polyalkyleneglycol is polyethylene glygol.
 5. The composition of claim 4 whereinsaid polyethylene glycol has a molecular weight of about 4,000.
 6. Thecomposition of claim 1 wherein said aqueous solution further comprisesan eye compatible pH buffer in an amount effective to buffer the pH ofsaid solution to about 7.4 to 8.2.
 7. The composition of claim 6 whereinsaid buffer is boric acid.
 8. The composition of claim 6 wherein saidbuffer is a combination of mono-sodium and di-sodium phosphates.
 9. Thecomposition of claim 1 wherein said aqueous solution further comprisesus to about 1 percent by weight of an eye compatible biocide.
 10. Thecomposition of claim 1 wherein said aqueous solution further comprisesup to about 5 percent by weight polyvinyl pyrrolidone.